ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.610C>A (p.Arg204Ser) (rs727504243)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554035 SCV000623792 uncertain significance Hypertrophic cardiomyopathy 2017-04-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 204 of the TNNI3 protein (p.Arg204Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TNNI3-related disease. Different missense substitutions at this codon (p.Arg204His and p.Arg204Cys) have been determined to be pathogenic (PMID: 15698845, 20569525, 23906401, 27532257, 18801787, 27895589). This suggests that the arginine residue is critical for TNNI3 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change that affects a residue important for protein function. This evidence indicates that the variant is pathogenic, but additional clinical and functional data data is needed to prove that conclusively. Therefore, this variant has been classified as a Variant of Uncertain Significance.

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